Deirdre Murphy SMACC DUB

–“Bad Blood “ Taylor Swift

“Now we got problems, and I don't think we can solve them.”

Limulus amoebocyte lysate

Inflammation Coagulation

Inflammation Coagulation

In the ICU there is a 32 y.o. man…

Type 1 DM

Septic shock, pneumonia

hypotensive, lactate 5.5 mmol/l

High dose vasopressor and inotrope

Progressive symmetrical duskiness of all limbs- necrosis of fingers and distal feet

Labs..

‘flu A

Pneumococcal urine antigen

FBE

Hb 138

WCC 1.07

Plats 7

Marked red cell crenation, L shifted toxic neutrophils Severe thombocytopenia

Thrombocytopenia

severity of illness marker

multifactorial

vs.

destruction

? production

Production13-60%Of prognostic significance

DestructionMarrow failureprimary or secondary (suppression)

Idiopathic aplastic anemia

Malnutrition

Sepsis

Drugs

MechanicalIABP, ECMO, CRRT

MicroangiopathicTTP, DIC, SBE, vasculitis

Drugs splenic pooling

PassiveSplenomegaly

Cell mediatedHaemophagocytosis

Platelets in sepsis

Rapidly localise to site of infection, and migrate to liver, lungs

Cell-cell contact- adhesion molecules

Antimicrobial proteins bind bateria and viruses

Toll like receptors - PAMPS

NET(osis)

Many mechanisms by which platelets in sepsis contribute to inflammation

NETs

Neutrophil Extracellular Traps

Novel pathway by which bacteria trapped in the vasculature

Slide courtesy of Dr Rob Andrews, Australian Centre Blood Diseases, Monash Uni

COAGs..INR 4.2

PT 40

aPTT 80

Fib 3.8

D Dimers 16.97

TCT normal (= no heparin)

INR 4.2

PT 40

aPTT 80

Fib 3.8

D Dimers 16.97

INR 4.2

PT 40

aPTT 80

Fib 3.8

D Dimers 16.97

Fibrinogen is an acute phase protein- high fibrinogen does not rule out

fibrinolysis

D.I.C.

Death Is Coming

DIC

Clinico-pathological diagnosis (like sepsis- not a distinct entity)

Fibrin deposition in organs- organ failure

Coagulopathy

Several scoring systems

Levi et al BJH 2009 145:24-33. Guidelines for the diagnosis and management of DIC

ISTH

D.I.C.

Presence of DIC associated with mortality

Increasing score

Repeated score clinically useful

Wada et al J Intensive Care 2014NETS can cause this

DIC

Treat the cause

Treatment

?Activated protein C

?Tissue factor pathway inhibitor

Avoid prothrombotics- tranexamic acid, prothrombinex

-FFP safe- balanced

? heparin

Other? ? AT replacement

No reduction in death

inc bleeding

A 52 y.o. female presents to the Emergency Deparment..

presented with confusion, nausea, abdominal pain and vomiting

in ED found to have renal impairment and abnormal labs

LabsHb 100

Hct 0.29

WCC 11.6

Plats 9

INR 1.1

PT 14.3

aPTT 29.2

Fib 4.4

haptoglobin <0.08

urea 27.8

creat 246

LDH 1635 u/l (n 120-250)

fragments

thrombocytopenia

keratocyte

helmet cell

schistocyte

microspherocytes

Fragmentation-schistocytes ++- helmet cells, triangular cells . Polychromasia.

Nucleated red cells

MAHA microangiopathic haemolytic anaemia

Thrombotic microangiopathies

Thrombocytopaenia Microangiopathic haemolysis (MAHA)+

What are TMAs? Thrombotic

microangiopathies

Primary

TTP HUS Complement mediated TMAs DITMAs Hereditary forms

Secondary

Severe hypertension Preeclampsia/ HELLP

DITMAS

Drug induced thrombotic micro-

angiopathies

e.g.

CNIs Cocaine

CTZ Quinine (may be

abrupt onset)

Diagnostic test

ADAMTS 13..

A Disintegrin And Metalloprotease with a ThrombSpondin Type 1 motif, member 13

The ADAMS family

Moake, Sem in Hematol, 2004 Moake, Sem in Hematol, 2004

Moake, Sem in Hematol, 2004

additional tests..

Stool microscopy : no EHEC

Shiga toxin negative No recent drugs

Dx TTP

Urgent Plasma Exchange

(mortality 90% untreated)

Rationale for treatment

Steroids

Meanwhile in ICU…

The intensivist on duty is worried about a patient on VA ECMO for acute myocarditis

The patient has just clotted their ECMO pump..

Pump Thrombosis

Noisy pump

intravascular haemolysis… renal failure

FBE

FBE Day 1 Day 2 Day 3 Day 4 Day 5

Hb 110 108 105 96 92

WCC 6.4 7.5 4.8 5.6 4.9

Plats 289 267 205 199 98

HIT

Rare, difficult to diagnose, heparin dependant pro-thrombotic disorder

Antibody to platelet factor 4

The HIT Iceberg

Assfalg et al. 2016. World Journal of Transplantation. HIT in solid organ transplant recipients.

Pre-test probability

4T score 6- intermediate probability

Heparin stopped and bivalirudin commenced

Shortly after commencement of bivalirudin patient complained of severe abdo pain and lactic acidosis.

Takeaways

DIC is a clinico-pathological syndrome with different clinical phenotypes (bleeding, massive bleeding, thrombotic)

Low platelets are common in critically ill and multifactorial

TTP, HIT are very uncommon disorders but should be considered in the right clinical setting as they can both frequently be fatal